A review of the applications of tissue microarray technology in understanding the molecular features of endometrial carcinoma.

OBJECTIVE: To review the literature regarding the use of tissue microarray (TMA) technology in understanding the biology, diagnosis and prognosis of endometrial carcinoma (EC). STUDY DESIGN: This review of TMA technology in EC was based on a large number of published articles. We focused on the use of TMA technology as a tool to gain insight in endometrial carcinogenesis and to validate data obtained from DNA microarrays, proteomics and cellular models. RESULTS: We summarized the technical aspects of the 37 articles that were reviewed. The number of EC cases in each series varied from 32-485 (median, 128). The number of cores ranged from 1-4 (median, 2), and the size of the cores ranged from 0.6-2 mm (median, 0.6 mm). Only 3 studies applied fluorescence in situ hybridization technology, while the remaining 34 studies used immunohistochemistry. CONCLUSION: TMA can help to establish new prognostic markers and to define protein biomarkers that help in differential diagnosis.

Loss of heterozygosity in endometrial carcinoma.

Inactivation of a tumor suppressor gene typically occurs in two steps, thus fulfilling Knudson hypothesis. One "hit" is frequently a point mutation or a small deletion. The other alteration is usually a large genomic loss of part of a gene, or even part of a chromosome, or the whole chromosome. However, it is not clear which of these two events occurs first. Loss of heterozygosity (LOH) analysis allows the identification of one of the 2 hits. Although microsatellite polymerase chain reaction is the technique most frequently used to assess LOH, other different approaches can also be used. The LOH can also be assessed by restriction fragment length polymorphism analysis, single strand conformation polymorphism analysis, oligonucleotide microarrays capable to simultaneously determine the genotype of thousands of single-nucleotide polymorphism (single-nucleotide polymorphism arrays), comparative genomic hybridization, multiplex amplification and probe hybridization, and multiplex ligation-dependent probe amplification. In this article, the authors review the results obtained with molecular analysis of LOH in the understanding of development and progression of endometrial carcinoma. Particular attention is given to: (1) the presence of widespread LOH in nonendometrioid carcinoma, probably reflecting the existence of chromosomal instability; and (2) specific LOH patterns associated with some clinicopathologic features.

Metastatic small cell carcinoma to the thyroid gland: a pathologic and molecular study demonstrating the origin in the urinary bladder.

Small cell carcinomas may occur in the thyroid gland. Infrequently, they are primary tumors, and have been interpreted as variants of medullary thyroid carcinoma. However, the vast majority of small cell carcinomas involving the thyroid gland are metastatic tumors. In some cases, demonstration of the primary tumor is not easy. An example of a small cell carcinoma metastatic to the thyroid is presented in this report. The primary tumor was a small cell carcinoma that occurred as a minor component in a transitional carcinoma of the urinary bladder. The microscopical and immunohistochemical features of both tumors, in the thyroid and the bladder, were identical. Moreover, both tumors exhibited an identical mutation in p53, as well as similar loss of heterozygosity at 10q23 and RASSF1A promoter hypermethylation, clearly indicating that the bladder tumor was the site for the primary tumor of the patient.